BACKGROUNDSpinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. METHODSWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. RESULTSIn the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P = 0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P = 0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONSAmong infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074.)

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Despite rapidly evolving knowledge about COVID 19 infection, routes of perinatal COVID 19 transmission and viral load in mother neonate dyad remain uncertain. Data were analysed to describe the clinicodemographic profile and viral load in neonates born to COVID 19 positive mothers. Of 2947 deliveries, 69 mothers were COVID 19 positive (2.3%), with 1 abortion, 2 macerated stillbirths and 2 fresh stillbirths as pregnancy outcomes. Of 65 tested neonates, 10.7% (7) were confirmed COVID 19 positive by RTPCR (reverse transcriptase-polymerase chain reaction). Viral load (cycle threshold, Ct of E, RDRp) in neonates was comparable with the Ct reported from adults; however, neonates had milder clinical manifestations. All 7 neonates who tested positive for COVID 19 were subsequently discharged. Six of the 7 neonates were asymptomatic and 1 neonate needed respiratory support (indication being prematurity) which resolved after 48 h. Maternal and neonatal comparison of Ct of E and RdRp gene was statistically non-significant (25.97 vs 19.68, p = 0.34 and 26.5 vs 25.0, p = 0.84). Viral loads of mothers with COVID 19 positive neonates compared with mothers with COVID 19 negative neonates for E and RdRp gene were also statistically non-significant (25 vs 27.19, p = 0.63 and 19.6 vs 27.6, p = 0.08). The majority (93%) of neonates tested later than 48 h (roomed in with mother and breastfed) tested negative. Conclusion: The study supports milder manifestation in COVID 19 positive neonates. Risk of transmission from COVID 19 positive mother to neonate by rooming-in and breastfeeding is low. In this study on a limited number of neonates, maternal viral load was not found to be associated with the positivity status or severity of the illness of neonate.

Introduction The COVID19 pandemic raises a major concern about its severity in pregnancy, fetomaternal outcomes and risk of vertical transmission.The Cycle threshold indicating the viral load can be a contributory factor towards modifying the management of such pregnant women. We report a retrospective descriptive study regarding the clinical course, fetomaternal outcomes of pregnant women with COVID19. Methodology This is a single-center, retrospective study performed in a tertiary care hospital for pregnant women with COVID-19 in India. The medical records of the all women who delivered in the Covid facility from May 5th 2020 to June 5th 2020 were reviewed independently. Data extracted from the records included demography, obstetric details, co morbidities, disease severity, investigations, management and information on neonates (birthweight, Apgar score, and perinatal complications).Statistical analysis was performed by the SPSS program for Windows, version 17.0(SPSS, Chicago, Illinois) Results Amongst 348 women(suspects) tested for SARS-CoV-2, 57 women ( 57/348,16.3%) were confirmed positive based on qRT-PCR of nasopharyngeal specimen. Most women (45 /78.9 %) had mild infection with favourable fetomaternal outcomes. Three maternal mortalities were associated with co morbidities. Five neonates tested positive for SARS-CoV-2, remained haemodynamically stable and were subsequently discharged. Conclusions Majority of pregnant women with Covid-19 had mild disease and recovered subsequently with good perinatal outcomes. Women with co morbidities may have increased risk of severe morbidity and mortality.The Cycle threshold signifying the viral load and degree of infectivity can modify the management during pregnancy.Long-term outcomes and the potential mother-to-child vertical/horizontal transmission needs further study.

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